Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery.

20:09 EST 20th December 2014 | BioPortfolio

Summary of "Posttraumatic reduction of edema with aquaporin-4 RNA interference improves acute and chronic functional recovery."

Traumatic brain injury (TBI) is common in young children and adolescents and is associated with long-term disability and mortality. The neuropathologic sequelae that result from juvenile TBI are a complex cascade of events that include edema formation and brain swelling. Brain aquaporin-4 (AQP4) has a key role in edema formation. Thus, development of novel treatments targeting AQP4 to reduce edema could lessen the neuropathologic sequelae. We hypothesized that inhibiting AQP4 expression by injection of small-interfering RNA (siRNA) targeting AQP4 (siAQP4) after juvenile TBI would decrease edema formation, neuroinflammation, neuronal cell death, and improve neurologic outcomes. The siAQP4 or a RNA-induced silencing complex (RISC)-free control siRNA (siGLO) was injected lateral to the trauma site after controlled cortical impact in postnatal day 17 rats. Magnetic resonance imaging, neurologic testing, and immunohistochemistry were performed to assess outcomes. Pups treated with siAQP4 showed acute (3 days after injury) improvements in motor function and in spatial memory at long term (60 days after injury) compared with siGLO-treated animals. These improvements were associated with decreased edema formation, increased microglial activation, decreased blood-brain barrier disruption, reduced astrogliosis and neuronal cell death. The effectiveness of our treatment paradigm was associated with a 30% decrease in AQP4 expression at the injection site.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.118.

Affiliation

1] Department of Physiology, Loma Linda University, Loma Linda, California, USA [2] Department of Pediatrics, Loma Linda University Medical Center, Loma Linda, California, USA.

Journal Details

This article was published in the following journal.

Name: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
ISSN: 1559-7016
Pages:

Links

PubMed Articles [14385 Associated PubMed Articles listed on BioPortfolio]

Brain edema in acute liver failure: mechanisms and concepts.

Brain edema and associated increase in intracranial pressure continue to be lethal complications of acute liver failure (ALF). Abundant evidence suggests that the edema in ALF is largely cytotoxic bro...

Mechanisms of Astrocyte-Mediated Cerebral Edema.

Cerebral edema formation stems from disruption of blood brain barrier (BBB) integrity and occurs after injury to the CNS. Due to the restrictive skull, relatively small increases in brain volume can t...

Cerebral Perfusion and Blood Pressure Do Not Affect Perihematoma Edema Growth in Acute Intracerebral Hemorrhage.

The pathogenesis of perihematoma edema in intracerebral hemorrhage (ICH) is unknown but has been hypothesized to be ischemic. In the ICH Acutely Decreasing Arterial Pressure Trial (ICH ADAPT), perihem...

Acute posttraumatic pediatric cerebral venous thrombosis: Case report and review of literature.

Pediatric cerebral venous thrombosis (CVT) is a common sequelae of infection, coagulopathies, and dehydration in the pediatric population. Acute posttraumatic CVT is an uncommon etiology of pediatric ...

Acute heart failure: acute cardiogenic pulmonary edema and cardiogenic shock.

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis an...

Clinical Trials [4427 Associated Clinical Trials listed on BioPortfolio]

Non Invasive Mechanical Ventilation in Acute Cardiogenic Pulmonary Edema

Cardiogenic pulmonary edema (CPE) is a common medical emergency and noninvasive ventilation (NIV) in addition to conventional medical treatment might be beneficial for patients with CPE.

Evaluation of Inflammatory Symptoms Reduction With Amoxicillin + Ketoprofen in Acute Pharyngeal- Tonsillitis in Pediatric Patients

The purpose of this study is to evaluate the inflammatory symptoms and signs (hyperemia, edema and pain) reduction after 24 hours of treatment with ketoprofen drops when associated to amox...

Treatment of Refractory Diabetic Macular Edema With Infliximab

The purpose of this study is to determine if treatment with infliximab improves macular edema which is refractory to laser photocoagulation in patients with diabetes.

Out-of-Hospital CPAP for Severe Cardiogenic Pulmonary Edema

In cardiogenic pulmonary edema, Continuous Positive Airway Pressure (CPAP) added to medical treatment improves outcome. The present study was designed to assess the benefit of CPAP as a fi...

BK Virus and Renal Dysfunction in Postoperative/Posttraumatic Critically Ill Patients

The purpose of this study is to find out whether acute renal failure is associated with BK virus reactivation in postoperative/posttraumatic critically ill patients with severe SIRS/sepsis...

Medical and Biotech [MESH] Definitions

Aquaporin 2 is a water-specific channel protein that is expressed in KIDNEY COLLECTING DUCTS. The translocation of aquaporin 2 to the apical PLASMA MEMBRANE is regulated by VASOPRESSIN, and MUTATIONS in AQP2 have been implicated in a variety of kidney disorders including DIABETES INSIPIDUS.

Abrupt reduction in kidney function defined as an absolute increase in serum CREATININE of more than or equal to 0.3. mg/dl, a percentage increase in serum creatinine of more than or equal to 50%, or a reduction in urine output. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.

Aquaporin 4 is the major water-selective channel in the CENTRAL NERVOUS SYSTEM of mammals.

Aquaporin 3 is an aquaglyceroporin that is expressed in the KIDNEY COLLECTING DUCTS and is constitutively localized at the basolateral MEMBRANE.

Aquaporin 6 is an aquaglyceroporin that is found primarily in KIDNEY COLLECTING DUCTS. AQP6 protein functions as an anion-selective channel.

Search BioPortfolio:
Loading
Advertisement

Relevant Topic

Alzheimer's Disease
Latest News Clinical Trials Research Drugs Reports Corporate
Of all the types of Dementia, Alzheimer's disease is the most common, affecting around 465,000 people in the UK. Neurons in the brain die, becuase  'plaques' and 'tangles' (mis-folded proteins) form in the brain. People with Al...

Advertisement